Development and validation of a novel CNS-penetrant radiotracer for exploring innate immune activation in murine multiple sclerosis

Samantha Reyes - Graduate Student, Stanford University

Detecting and staging pathological drivers of multiple sclerosis (MS), including neuroinflammation, is incredibly challenging. As a result, effective treatment and management of disease is suboptimal, thus impacting patient quality of life. Standard of care tests lack specificity and do not provide spatiotemporal information on immune cell phenotypes within the CNS. For example, blood draws can provide information on peripheral inflammatory markers (e.g., C-reactive protein) in addition to neuronal damage (neurofilament light chain protein), spinal punctures can verify the presence of oligoclonal bands, and MRI scans can give insights into structural changes related to demyelinating lesions. Positron emission tomography (PET) imaging on the other hand is an ideal modality to provide specific molecular information on neuroinflammation as radiotracers can be designed to target biomarkers associated with disease. For instance, radiotracers specific to translocator protein 18kDa (TSPO) have been widely evaluated for imaging neuroinflammation for over two decades. While TSPO-PET has shed light on immune cells, it lacks specificity, making the interpretation of the resulting images challenging. To address this shortcoming, there have been significant efforts to identify biomarkers that are highly specific to innate immune cell phenotypes. In this talk, I will summarize the key steps to developing and validating a novel CNS-penetrant radiotracer, from molecule selection to both in vitro and in vivo specificity validation and signal quantitation. Finally, I will discuss some exciting new data from a project I am leading on developing and validating radiotracers for GPR84, a novel target for identifying pro-inflammatory myeloid cells.

Development of LGAD detectors for X-ray and medical applications

Simone Mazza - Assistant Research Scientist, Santa Cruz Institute for Particle Physics (SCIPP) at UC Santa Cruz

Low Gain Avalanche Detectors (LGADs) are characterized by a fast rise time (~500ps), extremely good time resolution (down to 17ps), and the potential for a very high repetition rate with ~1 ns full charge collection. For the application of this technology to near future experiments such as e+e- Higgs factories (FCC-ee), the ePIC detector at the Electron-Ion Collider, or smaller experiments (e.g., the PIONEER experiment), the intrinsic low granularity of LGADs and the large power consumption of readout chips for precise timing is problematic. However, several new LGAD technologies allow for fine pixelization: AC-LGADs, TI-LGADs, DJ-LGADs, etc. Several uses outside of LGADs outside of HEP and NP are being explored by the international community; thanks to the fast timing and simplicity of design, LGADs could be employed in TOF PET and other medical applications. Furthermore, the intrinsic gain and fast collection time allow LGADs to be great solid-state low-energy X-ray detectors even in the fast repetition rate of cyclotron light sources. In this contribution, the LGAD technology will be introduced, and a number of foreseen applications will be presented.

Introducing Hamamatsu and its research on instrumentation for future PET

Ryosuke Ota - Research Scientist, Hamamatsu, UC Davis

Hamamatsu Photonics is a well-known Japanese optical company founded in 1953. All Hamamatsu's products are related to optics and span a wide range from small devices to large systems. Moreover, applications using the Hamamatsu products are highly diverse, from state-of-the-art particle physics experiments and quantum computers to more familiar technologies like LiDAR used for assisting autonomous driving. In the field of positron emission tomography (PET), photodetectors with photon counting capability, such as photomultiplier tubes (PMTs) and multipixel photon counters (MPPCs), are some of the most representative products from Hamamatsu. These photodetectors play an essential role in precise spatiotemporal detection of annihilation gamma rays in PET. Although they have been developed several decades or almost a century ago, there is still scope for performance improvement, which prompts us to seek their undiscovered potential. In this presentation, I will give a brief overview of Hamamatsu Photonics and our ongoing research in PET instrumentation on the photodetector, module, and system level carried out at the Central Research Laboratory of Hamamatsu and at UC Davis.

Novel imaging developments for radiation therapy

Qihui Lyu - UC San Francisco

Revolutionizing Autoradiography: Ultra-Thin Silicon 3D Radiopharmaceutical Tracker

Hyeyeun Chu - Graduate Student, Lawrence Berkeley National Lab

Conventional autoradiography methods rely on labor-intensive serial tissue slicing and registration processes, potentially obscuring three dimensional relationships of radionuclides in tumor microenvironment. In this work, we present a novel 3D radiopharmaceutical tracker (3D RPT) technique that alleviates these limitations by providing radionuclide positions in intact tissue samples at thicknesses of 100 um. Using two stacked ultra-thin CMOS sensors, this detector records charged-particle trajectories on an event-by-event basis, providing both depth information and enhanced 2D resolution. To demonstrate the feasibility and performance of 3D RPT, Monte Carlo simulations across various energies within tissue have been conducted. The basic detector configurations and performances from simulation will be presented.

By delivering cellular-level volumetric activity maps directly from intact tissues, the 3D RPT enables more precise absorbed dose calculations— which is crucial for refining radiopharmaceutical therapy strategies. This approach reveals potential dose heterogeneity in tumor microenvironment and elucidates reasons for suboptimal therapeutic outcomes, such as inadequate tracer uptake and limited particle penetration. Ultimately, this approach provides essential information for refining tracer design, selecting appropriate radionuclides, and optimizing dose, paving the way for more consistent and effective radiopharmaceutical therapy outcomes.